This proposal is part of a long-term effort to study the auditory system at the molecular level. The studies outlined in this application are designed to characterize both normal and pathological auditory nerve proteins with emphasis on rapidly turning-over glycoproteins (RTGP's) and hair cell-associated proteins (HAP's) RTGP's are a group of 5 or 6 rapidly transported proteins with similar molecular weights and isoelectric points that are degraded with half-lives of less than 2.5 h in auditory nerve terminals. HAP's are two proteins (or groups of proteins) rapidly transported in the auditory nerve whose expression appears to be dependent on the state of the hair cell. After damage to the hair cell in the waltzing guinea pig or animals treated with ototoxic drugs, the labeling of the HAP's in the auditory nerve increases more than sixfold. The present studies will include in vivo labeling and characterization to gain insight into the function of RTGP's and HAP's. The effect of hair cell damage by the ototoxic drug, neomycin, on proteins transported in the auditory nerve will be determined. Studies are designed to determine the biochemical properties of the RTGP's and HAP's and priovide data essential for their purification. The similar properties of the several forms of RTGP suggest a functional or biochemical relationship and it will be determined if the several forms are due to modifications of a single protein. To allow further characterization, the RTGP's and HAP's will be purified. Two methods of purification are proposed, one by standard techniques and the other with monoclonal antibodies. The purified proteins will be characterized with respect to gross and subcellular localization. Proteins specific for the auditory nerve will be identified and characterized with monoclonal antibodies. It will be determined if these proteins can be used as markers for Type I and Type II spiral ganglion cells.